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Increased cardiac remodeling in cardiac-specific Flt-1 receptor knockout mice with pressure overload

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Abstract

Vascular endothelial growth factor (VEGF) inhibition has previously been shown to have damaging effects on the heart. Because the role of Flt-1 (a phosphotyrosine kinase receptor for VEGF) in cardiac function and hypertrophy is unclear, we generated mice lacking Flt-1 only in their cardiomyocytes (Flt-1 KO). The hearts from 8- to 10-week–old mice were measured by using echocardiography and histology. No significant differences were seen in fraction shortening, cross-sectional area of cardiomyocytes, and interstitial collagen fraction between littermate controls and KO mice at baseline. To test the hypothesis that Flt-1 is involved in cardiac remodeling, we performed transverse aorta constriction (TAC) by ligating the transverse ascending aorta. Four weeks after TAC, echocardiography of the mice was performed, and the hearts were excised for pathological analysis and Western blotting. No difference in mortality was found between Flt-1 KO mice and controls; however, KO mice showed a greater cardiomyocyte cross-sectional area and interstitial collagen fraction than controls. Western blotting indicated that AKT was activated less in Flt-1 KO hearts after TAC compared with that in control hearts. Thus, Flt-1 deletion in cardiomyocytes increased hypertrophy, fibrosis, and regression of AKT phosphorylation. Our study suggests that Flt-1 plays a critical role in cardiac hypertrophy induced by pressure overload via the activation of AKT, which seems to be cardioprotective.

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Acknowledgements

This work was supported by Zhejiang Provincial Natural Science Foundation of China (LY14H020006) and by the National Natural Science Fund of China from Ning Zhou (81100087).

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The authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Oral Prophylaxis and Hygiene, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China, 325027

    Liqin Mei

  2. Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, People’s Republic of China, 325027

    Yinqing Huang, Jiafeng Lin, Maoping Chu & Lianpin Wu

  3. Department of Cardiology, Tongji Hospital of Tongji University, 309 Xincun Road, Putuo district, Shanghai, People’s Republic of China, 200065

    Chaohui Hu

  4. Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, People’s Republic of China, 430030

    Ning Zhou

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  1. Liqin Mei
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Correspondence to Lianpin Wu.

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Mei, L., Huang, Y., Lin, J. et al. Increased cardiac remodeling in cardiac-specific Flt-1 receptor knockout mice with pressure overload. Cell Tissue Res 362, 389–398 (2015). https://doi.org/10.1007/s00441-015-2209-5

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  • DOI: https://doi.org/10.1007/s00441-015-2209-5

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